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Gene Review

Slc10a1  -  solute carrier family 10 (sodium/bile acid...

Rattus norvegicus

Synonyms: Na(+)/bile acid cotransporter, Na(+)/taurocholate transport protein, Ntcp, Ntcp1, SBACT, ...
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Disease relevance of Slc10a1


High impact information on Slc10a1

  • Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na+-dependent taurocholate-cotransporting polypeptide and rat ileal apical Na+-dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT [3].
  • The perfused IBDUs absorbed TCA in a saturable, sodium-dependent manner; in addition, TCA absorption was blocked in a dose-dependent fashion by S0960, a specific inhibitor of the Na(+)/bile acid cotransporter [4].
  • RESULTS: LPS caused gene expression of the hepatocyte basolateral sodium-dependent taurocholate cotransporter (Ntcp) to decrease by more than 90% [5].
  • After deglycosylation of isolated basolateral rat liver plasma membranes, the apparent molecular weight of Ntcp decreased to 33,500 [6].
  • METHODS: A rabbit antiserum was raised against a fusion protein containing the maltose-binding protein and the C terminus of Ntcp [6].

Chemical compound and disease context of Slc10a1


Biological context of Slc10a1

  • Bile flow is rapidly and markedly reduced in hepatic inflammation, correlating with suppression of critical hepatic bile acid transporter gene expression, including the principal hepatic bile acid importer, the Na(+)/taurocholate co-transporting polypeptide (Ntcp, Slc10a1) [8].
  • Our findings suggest that Ntcp down-regulation during pregnancy occurs primarily at the transcriptional level [9].
  • METHODS: BA uptake and Ntcp expression were studied in control and timed-pregnant rats in late gestation [9].
  • Ntcp mRNA remained significantly elevated until 14 days postpartum but had begun to decline by 21 days postpartum [10].
  • Interleukin-1 beta-mediated suppression of RXR:RAR transactivation of the Ntcp promoter is JNK-dependent [8].

Anatomical context of Slc10a1


Associations of Slc10a1 with chemical compounds

  • RESULTS: A significantly reduced BA uptake and decreased Ntcp mRNA levels (-40%) and protein mass (-60%) was observed in pregnant rats [9].
  • These results are consistent with the hypothesis that the hepatic uptake of TC and E(2)17betaG is predominantly mediated by Ntcp and oatp1, respectively [11].
  • Cyclic AMP and cell swelling stimulate hepatic Na+/TC cotransport and Ntcp translocation via the phosphoinositide 3-kinase signaling pathway [15].
  • Also, estrogen administration to male rats decreases Ntcp expression [13].
  • Thus, these three peptides share the transporters that also recognize BQ-123 but appear to differ from Ntcp and oatp1 [14].

Physical interactions of Slc10a1

  • IL-1 beta predominates in a complex signaling network of Ntcp and Mrp2 regulation in cholestatic liver injury [1].

Regulatory relationships of Slc10a1

  • Protein kinase B/Akt mediates cAMP- and cell swelling-stimulated Na+/taurocholate cotransport and Ntcp translocation [15].

Other interactions of Slc10a1

  • Messenger RNA (mRNA) levels of transporters and binding activities as well as nuclear protein levels of Ntcp, Oatp2, and Mrp2 transactivators were determined 20 to 24 hours later [1].
  • Reduced mRNA levels (Ntcp, Oatp1, Oatp2) were associated with decreased transcriptional activities [16].
  • Protein levels declined only for Oatp4 (-50+/-17%) and Ntcp (-23+/-13%) at 24h [16].
  • Infusion of ovine prolactin (oPRL) to ovariectomized rats increased expression of both Ntcp and Bsep mRNA and protein [10].
  • In contrast, transfection with DN-PKB did not affect basal PKB activity, TC uptake, or Ntcp translocation [15].

Analytical, diagnostic and therapeutic context of Slc10a1


  1. Effects of proinflammatory cytokines on rat organic anion transporters during toxic liver injury and cholestasis. Geier, A., Dietrich, C.G., Voigt, S., Kim, S.K., Gerloff, T., Kullak-Ublick, G.A., Lorenzen, J., Matern, S., Gartung, C. Hepatology (2003) [Pubmed]
  2. Cytokine-independent repression of rodent Ntcp in obstructive cholestasis. Geier, A., Zollner, G., Dietrich, C.G., Wagner, M., Fickert, P., Denk, H., van Rooijen, N., Matern, S., Gartung, C., Trauner, M. Hepatology (2005) [Pubmed]
  3. Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter. Lazaridis, K.N., Pham, L., Tietz, P., Marinelli, R.A., deGroen, P.C., Levine, S., Dawson, P.A., LaRusso, N.F. J. Clin. Invest. (1997) [Pubmed]
  4. Perfused rat intrahepatic bile ducts secrete and absorb water, solute, and ions. Masyuk, A.I., Gong, A.Y., Kip, S., Burke, M.J., LaRusso, N.F. Gastroenterology (2000) [Pubmed]
  5. Regulation of hepatocyte bile salt transporters by endotoxin and inflammatory cytokines in rodents. Green, R.M., Beier, D., Gollan, J.L. Gastroenterology (1996) [Pubmed]
  6. In situ localization of the hepatocytic Na+/Taurocholate cotransporting polypeptide in rat liver. Stieger, B., Hagenbuch, B., Landmann, L., Höchli, M., Schroeder, A., Meier, P.J. Gastroenterology (1994) [Pubmed]
  7. Effect of Ursodeoxycholic Acid on the Expression of the Hepatocellular Bile Acid Transporters (Ntcp and bsep) in Rats With Estrogen-Induced Cholestasis. Micheline, D., Emmanuel, J., Serge, E. J. Pediatr. Gastroenterol. Nutr. (2002) [Pubmed]
  8. Interleukin-1 beta-mediated suppression of RXR:RAR transactivation of the Ntcp promoter is JNK-dependent. Li, D., Zimmerman, T.L., Thevananther, S., Lee, H.Y., Kurie, J.M., Karpen, S.J. J. Biol. Chem. (2002) [Pubmed]
  9. Down-regulation of the Na+/taurocholate cotransporting polypeptide during pregnancy in the rat. Arrese, M., Trauner, M., Ananthanarayanan, M., Pizarro, M., Solís, N., Accatino, L., Soroka, C., Boyer, J.L., Karpen, S.J., Miquel, J.F., Suchy, F.J. J. Hepatol. (2003) [Pubmed]
  10. Differential regulation of hepatic bile salt and organic anion transporters in pregnant and postpartum rats and the role of prolactin. Cao, J., Huang, L., Liu, Y., Hoffman, T., Stieger, B., Meier, P.J., Vore, M. Hepatology (2001) [Pubmed]
  11. Characterization of the transport properties of organic anion transporting polypeptide 1 (oatp1) and Na(+)/taurocholate cotransporting polypeptide (Ntcp): comparative studies on the inhibitory effect of their possible substrates in hepatocytes and cDNA-transfected COS-7 cells. Kouzuki, H., Suzuki, H., Stieger, B., Meier, P.J., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  12. The peptide-based thrombin inhibitor CRC 220 is a new substrate of the basolateral rat liver organic anion-transporting polypeptide. Eckhardt, U., Horz, J.A., Petzinger, E., Stüber, W., Reers, M., Dickneite, G., Daniel, H., Wagener, M., Hagenbuch, B., Stieger, B., Meier, P.J. Hepatology (1996) [Pubmed]
  13. Multihormonal regulation of hepatic sinusoidal Ntcp gene expression. Simon, F.R., Fortune, J., Iwahashi, M., Qadri, I., Sutherland, E. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  14. Carrier-mediated hepatic uptake of peptidic endothelin antagonists in rats. Akhteruzzaman, S., Kato, Y., Kouzuki, H., Suzuki, H., Hisaka, A., Stieger, B., Meier, P.J., Sugiyama, Y. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  15. Protein kinase B/Akt mediates cAMP- and cell swelling-stimulated Na+/taurocholate cotransport and Ntcp translocation. Webster, C.R., Srinivasulu, U., Ananthanarayanan, M., Suchy, F.J., Anwer, M.S. J. Biol. Chem. (2002) [Pubmed]
  16. Hepatobiliary organic anion transporters are differentially regulated in acute toxic liver injury induced by carbon tetrachloride. Geier, A., Kim, S.K., Gerloff, T., Dietrich, C.G., Lammert, F., Karpen, S.J., Stieger, B., Meier, P.J., Matern, S., Gartung, C. J. Hepatol. (2002) [Pubmed]
  17. Maternal cholestasis does not affect the ontogenic pattern of expression of the Na+/taurocholate cotransporting polypeptide (ntcp) in the fetal and neonatal rat liver. Arrese, M., Trauner, M., Ananthanarayanan, M., Boyer, J.L., Suchy, F.J. Hepatology (1998) [Pubmed]
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